The medicinal properties of acetylsalicylic acid have been known for millenia. The ancient Greeks noted that extracts of willow and poplar bark were effective painkillers, though it was not until the 1800s that its active ingredient, salicylic acid, was isolated. However, it was strongly acidic and irritated membranes of the mouth and stomach. In 1875, sodium salicylate was introduced in an attempt to weaken the salicylic acid, but it was found to be medically inefficient.
Above: The molecular structures of salicylic acid and sodium salicylate
In 1893, Felix Hoffman Jr. discovered a way to synthesize an ester of salicylic acid for Bayer Laboratories in Germany, acetylsalicylic acid. It was not as strong as salicylic acid but had the same medicinal properties. Acetylsalicylic acid was then patented in 1899 and became commercially available in 1915 under the name of Aspirin.
Left: The molecular structure of acetylsalicylic acid, commonly known as aspirin.
Today, Aspirin is one of the most commonly used drugs in the world. It is a powerful as a pain reliever, fever reducer, and swelling-reducing drug. It also reduces the clotting of blood and can be used in small doses to prevent heart attack and stroke. However, in some cases, it may still cause irritation to the stomach membranes, and blood in the stomach lining is lost due to the consumption of aspirin. The drug may also interfere with normal blood clotting and cause Reye's syndrome in children.
Above: An esterification reaction, which forms aspirin as one of its products.
In this experiment, it will be attempted to first prepare aspirin by chemical synthesis from salicylic acid, by acetylation with acetic anhydride. This synthesis is an esterification reaction between an ester and an acid to form a more complex ester. Esters are a type of acid in which the hyrdroxide groups are replaced with alkyl chains composed of carbon and hydrogen. Afterwards the product will be recrystallized to purify the product by allowing large, pure crystals to form by cooling slowly. Generally, the amount of product exceeds the amount of impurity, therefore the crystals of the product will form first and leave a greater ratio of impurity in the solution. Finally melting point and percentage yield will be determined in order to determine the purity of the aspirin.
Materials
Chemicals
Acetic anhydride
Salicylic acid (solid)
Sulphuric acid (Note: sulfuric acid will result in a lower yield, being a strong oxidizer. However sulfuric acid is still used sometimes for reactions that require the loss of water because it absorbs water while phosphoric acid does not.)
Ice
Distilled water
Ethyl alcohol
Equipment
Safety
Goggles
Containers
Large beaker (~600mL)
Smaller beaker (~100mL)
Large test tube
Measuring Devices
Balance
Graduated cylinder
Thermometer
Dropper
Other Equipment
Hot plate
Scoopula
Melttemp apparatus and at least four capillary tubes
Stirring rod
Watch glass
Buchner funnel
At least two pieces filter paper
Wash bottle
Dessicator with silica
Above: Dessicator with silica.
Above: Melttemp apparatus.
Procedure
Synthesis of Aspirin
Heat a large beaker full of water on the hot plate to 75-85˚C. Leave the hot plate on and the beaker on the hot plate for step 5.
Meanwhile, weigh out 3.0 g of salicylic acid and deposit in a large test tube.
Using a graduated cylinder, measure 6.0 mL of acetic anhydride and deposit into the test tube.
Add 10 drops of 85% sulphuric acid to the flask and stir with a stirring rod. The acid will act as a catalyst to speed up the reaction.
Place test tube in the large heated beaker of water on the hot plate, stirring occasionally for about 10 minutes.
Crystalizing the Aspirin
Remove beaker from heat. Using the dropper, carefully add 20 drops of cold distilled water to the test tube.
Allow the mixture to cool to room temperature so that crystals may form slowly.
Cool the mixture further by placing the test tube in a large beaker full of ice water to crystallize and minimize solubility for around 15 minutes, or until crystallization is complete. If crystallization does not start, tap the test tube with a stirring rod.
Meanwhile, weigh the filter paper with a watch glass and fill a wash bottle with around 25 mL of chilled distilled water to wash the crystals. Cool water must be used because warm water will dissolve the crystals.
Filter the solid aspirin through filter paper with a Buchner funnel and aspirator.
Rinse the crystals and test tube with the chilled water. At this point, impurities will still remain in the aspirin, necessitating recrystallization afterwards.
Place filter with product in a watch glass to dry overnight.
Weigh and measure the melting point range of the crude aspirin twice(see section below on finding the melting point).
Above: Filtering the solid aspirin using a Buchner funnel and aspirator.
Above: Crude aspirin.
Recrystallizing the Crude Aspirin
Dissolve crude aspirin in 10 mL of 95% ethyl alcohol in a 100 mL beaker.
Warm the mixture in a hot water bath on a hot plate to encourage dissolving. Note: Ethanol boils at 78˚C. DO NOT LET THE MIXTURE BOIL.
If the mixture does not dissolve, add an additional 2 mL of ethyl alcohol.
When all the aspirin has dissolved, pour in 10 mL of lukewarm distilled water until solution becomes transparent.
Cover the beaker with a watch glass and set aside to cool slowly undisturbed overnight so large crystals may form.
If an "oil" appears instead of a solid, reheat the beaker in hot water until the oil disappears. Repeat step 5. If crystals still do not appear, scratch the bottom of the beaker with a stirring rod to induce crystallization.
Collect crystals using vacuum filtering.
Rinse collected crystals with cold distilled water.
Allow the crystals to dry using vacuum filtering. If necessary, use a dessicator to dry out the aspirin.
At this time it is appropriate to weigh the purer aspirin sample and calculate the percentage yield out of a maximum yield of 3.9g again.
Above: Dissolving crude aspirin in ethyl alcohol.
Finding the Melting Point Range
Place about 5 mm of aspirin crystals into a capillary tube, which is then placed into the melttemp apparatus.
Insert a mercury thermometer through the top.
Heat the apparatus until 15˚C from the expected melting point (135˚C) at which temperature the heat should be reduced.
Record the range of the melting point as the temperature at which the first drop of liquid appears up to when all the aspirin has been converted into a liquid.
Repeat the process once more to find the melting point range.
Above: View through a melttemp apparatus. Here the aspirin crystals are solid.
Safety Precautions
Acetic Anhydride
Acetic anhydride is an irritant and also flammable, therefore gloves and goggles should be worn at all times during the experiment. It is reactive to water, so in the case of fire, alcohol foam or carbon dioxide is preferred to use as an extinguisher. This chemical has harmful fumes and use of a fume hood is strongly recommended.
Sulphuric and Salicylic Acid
These acids may irritate the skin in high concentrations. Take appropriate care to avoid contact.
Heating
Handle all hot equipments with caution and never leave the Bunsen burner flame unattended. The hot beakers and test tubes must be handled with care and should only be moved using tongs. Also, tie back long hair to prevent any accidental fire, and be familiar with the location of the fire extinguisher.
Observations
Mass of Aspirin Synthesized
Mass of Watch Glass and Filter Paper (g)
Mass of Watch Glass, Filter Paper, and Product (g)
Mass of Product (g)
Crude Product
48.572
45.612
2.964
Final Product
48.561
51.231
2.670
Melting Point
Trial
First Appearance of Liquid (˚C)
Completely Melted (˚C)
Crude 1
119
124
Crude 2
116
122
Crude Average
117.5
123
Final 1
129
137
Final 2
130
138
Final Average
129.5
137.5
Theoretical Melting Range
134
136
Above: The final product.
Calculations
Percentage Yield
Maximum Yield
Moles of a molecule = (Mass of substance) / (Molar mass)
Acetic Anhydride (C4H6O3): 102.09 g/mol, thus there are 6 g / 102.09 g/mol = 0.05877 moles
Salicylic Acid (C7H6O3): 138.12 g/mol, thus there are 3 g / 138.12 g/mol = 0.02172 moles
Aspirin (C9H8O4): 180.16 g/mol
Acetic Acid (C2H4O2): 60.05 g/mol
The balanced equation is
C4H6O3 + C7H6O3 → C9H8O4 + C2H4O2
which can also be written as
C6H4OHCOOH + (CH3CO)2O → C9H8O4 + CH3COOH
to show the molecular structure of aspirin more clearly.
Equal amounts of acetic anhydride and salicylic acid are required for this reaction, therefore salicylic acid is the limiting reagent.
Therefore only 0.02172 moles of aspirin will be produced.
Moles of a molecule = (Mass of substance) / (Molar mass)
Therefore,
Mass of a substance = (Moles of a substance) * (Molar mass)
180.16 g/mol x 0.02172 mol = 3.913g aspirin
Therefore the percentage yield for this synthesis of aspirin may be calculated as follows:
Crude Product
Maximum yield = 3.913 g
Actual yield = 2.96 g
Percentage yield = Actual yield / Maximum yield = 75.65%
Final Product
Maximum yield = 3.913 g
Actual yield = 2.67 g
Percentage yield = Actual yield / Maximum yield = 68.23%
Melting Range Percentage Error
As the melting point is a range, the average value of the range will be found before calculating percentage error.
Percentage error is calculated as |Theoretical value - Actual value| / Theoretical value.
Crude Product
Average of actual melting range = 120.25°C
Expected melting point = 135°C
Percentage error = |135 - 120.25| / 135 = 0.1093 = 10.93%
Final Product
Average of actual melting range = 133.5°C
Expected melting point = 135°C
Percentage error = |135 - 133.5| / 135 = 0.0111 = 1.11%
Conclusion and Analysis
The main purpose of this lab is to obtain aspirin by chemical synthesis from salicylic acid by acetylation with acetic anhydride and crystallization.Crystallization is the process of arranging atoms or molecules in a liquid state into an ordered solid state. During this process, the sample that is composed of more than one substance is transformed into new samples, each of which consists of a single substance. Thus a pure sample of the compound is obtained.
In our experiment, pure aspirin were obtained after filtering out the impurities and excess reagent through filter paper. A method to check a solid compound's purity after re-crystallization is to check its melting point. Impurities will always lower the melting point of a sample. In our experiment, the melting point range of the product was observed to be 129.5°C to 137.5°C. The percentage yield of the final product was calculated to be 68.23%.
It can be concluded that by recrystallizing the crude aspirin, though it decreased the percentage yield from 75.65% to 68.23%,a significantly purer aspirin was produced, as shown by the more feasible and realistic melting range. Aspirin has a theoretical melting range of 134-136°C. The crude product had a melting range of 117.5-123°C, and the final product one of 129.5-137.5°C. The percentage error of the crude product was 10.93%, while that of the final product was significantly lower at 1.11%.
Above: The 3D molecular structures of aspirin
By recrystalizing the crude aspirin slowly, it was possible to obtain large crystals with a rigorous structure by allowing the aspirin molecules to join together in a precise manner. The regular molecular crystal structure of the final product makes it more difficult for impurities to be included, eliminating many impurities present in the amorphous crude product.
Discussion
The synthesis of aspirin demonstrated here demonstrates several relevant suggestions that should be considered in the synthesis of a substance.
Firstly, the recrystallization of a product should be performed if possible and relevant. In most reactions, the amount of product exceeds the impurities. As a result, the crystals of the product should form first by virtue of greater volume. The remaining solution will be left with a greater concentration of impurities.
Secondly, melting point is a useful method of determining the purity of a product. When the theoretical melting range of a product is known, the melting range of a final product is usually narrower and closer to the theoretical melting range than the melting range of the crude product.
Finally for practical purposes, it is suggested that a beaker rather than a test tube be used in the synthesis of aspirin. Although a slanted test tube reduced the evaporation of reactants during the synthesis of aspirin, it was later found that the thin shape of the test tube made it difficult to seperate the product from the sides of the container using a scoopula.
Suggested Modifications to Procedure
If possible, when determining the melting point, the temperature should rise at a rate of 1-2°C per minute when nearing the expected melting point in order to acquire a more accurate range. The humidity of the lab should be kept at a minimum, as acetic anhydride, a reactant in the synthesis of aspirin, tends to react with water vapour to form acetic acid.
Phosphoric acid can be used instead of sulfuric acid if desired to obtain a higher yield, as sulfuric acid reacts more readily with the organic molecules involved in the reaction than phosphoric acid. However phosphoric acid does not absorb the water in the reaction, thus it may be a slower process.
Sources of Experimental Error
As in all experiments, experimental error is inevitably present, yielding inaccurate results. The complexity of this experiment only increases the possibility of the entrance of an unforseenable and/or uncontrollable variable. This section aims to present the sources and implications of these variables.
During the course of the experiment, it was possible that the thermometer inaccurately measured the melting range of the aspirin, being non-digital in operation. Exact values and decimal points could not be visually obtained; however, it is believed that the mercury thermometer was fairly functional and accurate. The melttemp apparatus, however, limited accuracy and precision of the melting range made it very difficult to control the pace of heating of the sample to small increments of 1-2°C per minute.
Secondly, the digital scale was also a potential source of error, as it was extremely sensitive and results were easily disturbed by small fluctuations such as the flow of air in the lab. The scale was also neither calibrated nor standardized. The masses of the products or reactants are subject to such uncontrollable fluctuations. As the amounts of reactants and aspirin synthesized were relatively small, even minor fluctuations can translate into multiple percentages in error.
Thirdly, impurities in the reactants or the aspirin could not be isolated, controlled, or eliminated apart from qualitatively during recrystallization. The lab in which the experiment was performed nor the cupboard in which the product was dried are unlikely to be sterile, therefore impurities could have entered the reaction or reactants at any time, especially since the containers used in the experiment were largely left open. Both acetic anhydride and acetylsalicylic acid decompose in humid air, which reduced percentage yield. Another possible source of contamination was the lab equipments used in this experiment. Although all the lab equipments were previously rinsed with water and dried, it is possible that chemical residue from previous experiments were present during the course of the experiment.
Fourthly, because sulfuric acid was used instead of phosphoric acid as a catalyst to synthesize aspirin, the percentage yield was quite low. This occurs because sulfuric acid reacts more strongly with the organic molecules in the reaction than phosphoric acid. However, it was still used because the synthesis of asprin entailed the absorbtion of water. Phosphoric acid does not absorb water, however sulfuric acid does. This property is called hygroscopy, and extends to dessicators such as calcium chloride and, to a lesser extent, silica, which was used to dry the aspirin prior to testing the melting point of the crude product.
The final draft may be found at http://vinstan.wikispaces.com/The+Synthesis+of+Aspirin
Synthesis of Aspirin.pdf
Powerpoint Presentation
Table of Contents
Introduction
The medicinal properties of acetylsalicylic acid have been known for millenia. The ancient Greeks noted that extracts of willow and poplar bark were effective painkillers, though it was not until the 1800s that its active ingredient, salicylic acid, was isolated. However, it was strongly acidic and irritated membranes of the mouth and stomach. In 1875, sodium salicylate was introduced in an attempt to weaken the salicylic acid, but it was found to be medically inefficient.Above: The molecular structures of salicylic acid and sodium salicylate
In 1893, Felix Hoffman Jr. discovered a way to synthesize an ester of salicylic acid for Bayer Laboratories in Germany, acetylsalicylic acid. It was not as strong as salicylic acid but had the same medicinal properties. Acetylsalicylic acid was then patented in 1899 and became commercially available in 1915 under the name of Aspirin.
Left: The molecular structure of acetylsalicylic acid, commonly known as aspirin.
Today, Aspirin is one of the most commonly used drugs in the world. It is a powerful as a pain reliever, fever reducer, and swelling-reducing drug. It also reduces the clotting of blood and can be used in small doses to prevent heart attack and stroke. However, in some cases, it may still cause irritation to the stomach membranes, and blood in the stomach lining is lost due to the consumption of aspirin. The drug may also interfere with normal blood clotting and cause Reye's syndrome in children.
Above: An esterification reaction, which forms aspirin as one of its products.
In this experiment, it will be attempted to first prepare aspirin by chemical synthesis from salicylic acid, by acetylation with acetic anhydride. This synthesis is an esterification reaction between an ester and an acid to form a more complex ester. Esters are a type of acid in which the hyrdroxide groups are replaced with alkyl chains composed of carbon and hydrogen. Afterwards the product will be recrystallized to purify the product by allowing large, pure crystals to form by cooling slowly. Generally, the amount of product exceeds the amount of impurity, therefore the crystals of the product will form first and leave a greater ratio of impurity in the solution. Finally melting point and percentage yield will be determined in order to determine the purity of the aspirin.
Materials
Chemicals
Equipment
Safety
Containers
Measuring Devices
Other Equipment
Above: Dessicator with silica.
Above: Melttemp apparatus.
Procedure
Synthesis of Aspirin
Crystalizing the Aspirin
Above: Filtering the solid aspirin using a Buchner funnel and aspirator.Above: Crude aspirin.
Recrystallizing the Crude Aspirin
Above: Dissolving crude aspirin in ethyl alcohol.Finding the Melting Point Range
Above: View through a melttemp apparatus. Here the aspirin crystals are solid.
Safety Precautions
Acetic Anhydride
Acetic anhydride is an irritant and also flammable, therefore gloves and goggles should be worn at all times during the experiment. It is reactive to water, so in the case of fire, alcohol foam or carbon dioxide is preferred to use as an extinguisher. This chemical has harmful fumes and use of a fume hood is strongly recommended.Sulphuric and Salicylic Acid
These acids may irritate the skin in high concentrations. Take appropriate care to avoid contact.Heating
Handle all hot equipments with caution and never leave the Bunsen burner flame unattended. The hot beakers and test tubes must be handled with care and should only be moved using tongs. Also, tie back long hair to prevent any accidental fire, and be familiar with the location of the fire extinguisher.Observations
Mass of Aspirin Synthesized
Melting Point
Above: The final product.Calculations
Percentage Yield
Maximum Yield
Moles of a molecule = (Mass of substance) / (Molar mass)Acetic Anhydride (C4H6O3): 102.09 g/mol, thus there are 6 g / 102.09 g/mol = 0.05877 moles
Salicylic Acid (C7H6O3): 138.12 g/mol, thus there are 3 g / 138.12 g/mol = 0.02172 moles
Aspirin (C9H8O4): 180.16 g/mol
Acetic Acid (C2H4O2): 60.05 g/mol
The balanced equation is
C4H6O3 + C7H6O3 → C9H8O4 + C2H4O2
which can also be written as
C6H4OHCOOH + (CH3CO)2O → C9H8O4 + CH3COOH
to show the molecular structure of aspirin more clearly.
Equal amounts of acetic anhydride and salicylic acid are required for this reaction, therefore salicylic acid is the limiting reagent.
Therefore only 0.02172 moles of aspirin will be produced.
Moles of a molecule = (Mass of substance) / (Molar mass)
Therefore,
Mass of a substance = (Moles of a substance) * (Molar mass)
180.16 g/mol x 0.02172 mol = 3.913g aspirin
Therefore the percentage yield for this synthesis of aspirin may be calculated as follows:
Crude Product
Maximum yield = 3.913 gActual yield = 2.96 g
Percentage yield = Actual yield / Maximum yield = 75.65%
Final Product
Maximum yield = 3.913 gActual yield = 2.67 g
Percentage yield = Actual yield / Maximum yield = 68.23%
Melting Range Percentage Error
As the melting point is a range, the average value of the range will be found before calculating percentage error.Percentage error is calculated as |Theoretical value - Actual value| / Theoretical value.
Crude Product
Average of actual melting range = 120.25°CExpected melting point = 135°C
Percentage error = |135 - 120.25| / 135 = 0.1093 = 10.93%
Final Product
Average of actual melting range = 133.5°CExpected melting point = 135°C
Percentage error = |135 - 133.5| / 135 = 0.0111 = 1.11%
Conclusion and Analysis
The main purpose of this lab is to obtain aspirin by chemical synthesis from salicylic acid by acetylation with acetic anhydride and crystallization.Crystallization is the process of arranging atoms or molecules in a liquid state into an ordered solid state. During this process, the sample that is composed of more than one substance is transformed into new samples, each of which consists of a single substance. Thus a pure sample of the compound is obtained.
In our experiment, pure aspirin were obtained after filtering out the impurities and excess reagent through filter paper. A method to check a solid compound's purity after re-crystallization is to check its melting point. Impurities will always lower the melting point of a sample. In our experiment, the melting point range of the product was observed to be 129.5°C to 137.5°C. The percentage yield of the final product was calculated to be 68.23%.
It can be concluded that by recrystallizing the crude aspirin, though it decreased the percentage yield from 75.65% to 68.23%,a significantly purer aspirin was produced, as shown by the more feasible and realistic melting range. Aspirin has a theoretical melting range of 134-136°C. The crude product had a melting range of 117.5-123°C, and the final product one of 129.5-137.5°C. The percentage error of the crude product was 10.93%, while that of the final product was significantly lower at 1.11%.
Above: The 3D molecular structures of aspirin
By recrystalizing the crude aspirin slowly, it was possible to obtain large crystals with a rigorous structure by allowing the aspirin molecules to join together in a precise manner. The regular molecular crystal structure of the final product makes it more difficult for impurities to be included, eliminating many impurities present in the amorphous crude product.
Discussion
The synthesis of aspirin demonstrated here demonstrates several relevant suggestions that should be considered in the synthesis of a substance.Firstly, the recrystallization of a product should be performed if possible and relevant. In most reactions, the amount of product exceeds the impurities. As a result, the crystals of the product should form first by virtue of greater volume. The remaining solution will be left with a greater concentration of impurities.
Secondly, melting point is a useful method of determining the purity of a product. When the theoretical melting range of a product is known, the melting range of a final product is usually narrower and closer to the theoretical melting range than the melting range of the crude product.
Finally for practical purposes, it is suggested that a beaker rather than a test tube be used in the synthesis of aspirin. Although a slanted test tube reduced the evaporation of reactants during the synthesis of aspirin, it was later found that the thin shape of the test tube made it difficult to seperate the product from the sides of the container using a scoopula.
Suggested Modifications to Procedure
If possible, when determining the melting point, the temperature should rise at a rate of 1-2°C per minute when nearing the expected melting point in order to acquire a more accurate range. The humidity of the lab should be kept at a minimum, as acetic anhydride, a reactant in the synthesis of aspirin, tends to react with water vapour to form acetic acid.Phosphoric acid can be used instead of sulfuric acid if desired to obtain a higher yield, as sulfuric acid reacts more readily with the organic molecules involved in the reaction than phosphoric acid. However phosphoric acid does not absorb the water in the reaction, thus it may be a slower process.
Sources of Experimental Error
As in all experiments, experimental error is inevitably present, yielding inaccurate results. The complexity of this experiment only increases the possibility of the entrance of an unforseenable and/or uncontrollable variable. This section aims to present the sources and implications of these variables.During the course of the experiment, it was possible that the thermometer inaccurately measured the melting range of the aspirin, being non-digital in operation. Exact values and decimal points could not be visually obtained; however, it is believed that the mercury thermometer was fairly functional and accurate. The melttemp apparatus, however, limited accuracy and precision of the melting range made it very difficult to control the pace of heating of the sample to small increments of 1-2°C per minute.
Secondly, the digital scale was also a potential source of error, as it was extremely sensitive and results were easily disturbed by small fluctuations such as the flow of air in the lab. The scale was also neither calibrated nor standardized. The masses of the products or reactants are subject to such uncontrollable fluctuations. As the amounts of reactants and aspirin synthesized were relatively small, even minor fluctuations can translate into multiple percentages in error.
Thirdly, impurities in the reactants or the aspirin could not be isolated, controlled, or eliminated apart from qualitatively during recrystallization. The lab in which the experiment was performed nor the cupboard in which the product was dried are unlikely to be sterile, therefore impurities could have entered the reaction or reactants at any time, especially since the containers used in the experiment were largely left open. Both acetic anhydride and acetylsalicylic acid decompose in humid air, which reduced percentage yield. Another possible source of contamination was the lab equipments used in this experiment. Although all the lab equipments were previously rinsed with water and dried, it is possible that chemical residue from previous experiments were present during the course of the experiment.
Fourthly, because sulfuric acid was used instead of phosphoric acid as a catalyst to synthesize aspirin, the percentage yield was quite low. This occurs because sulfuric acid reacts more strongly with the organic molecules in the reaction than phosphoric acid. However, it was still used because the synthesis of asprin entailed the absorbtion of water. Phosphoric acid does not absorb water, however sulfuric acid does. This property is called hygroscopy, and extends to dessicators such as calcium chloride and, to a lesser extent, silica, which was used to dry the aspirin prior to testing the melting point of the crude product.